Catalase produced by Candida albicans protects Streptococcus mutans from H 2 O 2 stress—one more piece in the cross-kingdom synergism puzzle

Abstract

ABSTRACT Co-infection with Streptococcus mutans and Candida albicans is associated with dental caries, and their co-cultivation results in enhanced biofilm matrix production that contributes to increased virulence and caries risk. Moreover, the catalase-negative S. mutans demonstrates increased oxidative stress tolerance when co-cultivated in biofilms with C. albicans, a catalase-producing yeast. Here, we sought to obtain mechanistic insights into the increased H 2 O 2 tolerance of S. mutans when co-cultivated with clinical isolates of Candida glabrata , Candida tropicalis, and C. albicans . Additionally, the C. albicans SC5314 laboratory strain, its catalase mutant (SC5314 Δcat1 ), and S. mutans UA159 and its glucosyltransferase B/C mutant (UA159 ΔgtfB/C ) were grown as single- and dual-species biofilms. Time-kill assays revealed that upon acute H 2 O 2 challenge, the survival rates of S. mutans in dual-species biofilms with the clinical isolates and C. albicans SC5314 were greater than when paired with SC5314 Δcat1 or as a single-species biofilm. Importantly, this protection was independent of glucan production through S. mutans GtfB/C. Transwell assays and treatment with H 2 O 2 -pre-stimulated C. albicans SC5314 supernatant revealed that this protection is contact-dependent. Biofilm stability assays with sublethal H 2 O 2 or peroxigenic Streptococcus A12 challenge resulted in biomass reduction of single-species S. mutans UA159 and dual-species with SC5314 Δcat1 biofilms compared to UA159 biofilms co-cultured with C. albicans SC5314. S. mutans oxidative stress genes were upregulated in single-species biofilms when exposed to H 2 O 2, but not when S. mutans was co-cultivated with C. albicans SC5314. Here, we uncovered a novel, contact-dependent, synergistic interaction in which the catalase of C. albicans protects S. mutans against H 2 O 2 . IMPORTANCE It is well established that co-infection with the gram-positive caries-associated bacterium Streptococcus mutans and the yeast pathobiont Candida albicans results in aggressive forms of caries in humans and animal models. Together, these microorganisms form robust biofilms through enhanced production of extracellular polysaccharide matrix. Further, co-habitation in a biofilm community appears to enhance these microbes’ tolerance to environmental stressors. Here, we show that catalase produced by C. albicans protects S. mutans from H 2 O 2 stress in a biofilm matrix-independent manner. Our findings uncovered a novel synergistic trait between these two microorganisms that could be further exploited for dental caries prevention and control.